The administration of chemotherapy at the earliest time (neoadjuvant or induction chemotherapy) following diagnosis in an effort to reduce the risk of disease recurrence in patients with non-small cell lung cancer (NSCLC) is under investigation at multiple institutions in the U.S., Europe, and Japan. This approach has resulted in radiographic response rates of 56-70% with complete remission rates of 1-8% and partial remission rates of 55-64% in patients with stage IB-IIIA with 2-3 cycles of platinum plus gemcitabine, paclitaxel, or docetaxel. Patients with pathologically proven N2 disease prior to chemotherapy had negative N2 nodes on resection in 50% of cases. A complete pathologic remission has been documented in 6-16% of patients (95% Cl, 0-23%). Disease progression during treatment has been observed in 2-10% of patients, and a complete surgical resection was achieved in 70-92% of patients. It is important to devise less toxic, yet efficacious regimens that are well tolerated and can be given expeditiously so as to allow surgery to be done in a timely fashion. Neoadjuvant therapy allows for investigations of molecular parameters that may affect response to chemotherapy and patients' survival. It is our hypothesis that the expression of genes associated with activation, inactivation, and efficacy of the drugs gemcitabine and pemetrexed will predict response to therapy and prognosis. We further hypothesize that the expression of these genes will be altered during chemotherapy. We propose a phase II study of neoadjuvant chemotherapy with gemcitabine and pemetrexed in patients with resectable NSCLC, specifically correlating molecular parameters to the primary clinical study endpoint disease response (radiographic CR+PR) and the secondary endpoints complete pathological response at surgery, disease-free survival, and overall survival. [unreadable] [unreadable]